Obstructive sleep apnea (OSA) afflicts 20 million adults in the United States, and is associated with increased morbidity and mortality. Major male-female differences in the incidence and co-morbidities of the disorder are poorly understood. However, in preliminary studies, we found gender differences in the location and extend of neural injury associated with OSA. Since brain changes occurring with OSA may contribute to physiologic and neuropsychological characteristics, male-female differences could explain some of the gender differences in the disorder. Before attempting to related neural changes to comprehensive measures of health status, we aim to verify the gender differences in neural injury associated with OSA. We will assess 64 subjects with and without OSA, split evenly between males and females;all OSA subjects will be recently diagnosed and untreated for the sleep disorder. We will assess whole-brain structure with diffusion tensor imaging indices (fractional anisotropy and mean diffusivity), T2 relaxation time, and regional gray matter volume measures, modeled by gender and OSA status, and other potentially significant effects (sex, age, body mass index) and two-way interactions. We will additionally assess neural influences of depressive symptoms as measure by the Beck Depression Inventory-II, and OSA severity (apnea-hypopnea index). The findings will establish which brain areas show large male-female differences in neural injury associated with OSA;the functional roles of the particular structures affected will be used in future studies to select relevant health status measurements. For example, if depression-related regions are affected, follow-on studies will include comprehensive assessment of mental health status. Understanding the role of gender in brain injury occurring with OSA is important for understanding syndrome progression and development of co-morbidities, and for considering different treatment strategies for male and female patients. PUBLIC HEALTH RELEVANCE: This study will compare the brain damage between men and women with Obstructive Sleep Apnea (OSA), a sleep illness that leads to poor health and early death. We will use magnetic resonance imaging to see whether there is more or less brain injury in males than females. We will look at specific brain regions that are related to the problems that women but not men with OSA have, such as depression. If there are important differences between the sexes in the amount of damage, and places in the brain that are affected, our future studies will look to see if those brain changes explain the male-female health differences we see in OSA.